rs242936

Positions:

• chr17-45821843-A-G
• chr17-45821843-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000314537.10(CRHR1):​c.327+403A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.896 in 152,292 control chromosomes in the GnomAD database, including 61,173 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.90 (61173 hom., cov: 34)
• Consequence: CRHR1 ENST00000314537.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245

Genes affected

CRHR1 (HGNC:2357): (corticotropin releasing hormone receptor 1) This gene encodes a G-protein coupled receptor that binds neuropeptides of the corticotropin releasing hormone family that are major regulators of the hypothalamic-pituitary-adrenal pathway. The encoded protein is essential for the activation of signal transduction pathways that regulate diverse physiological processes including stress, reproduction, immune response and obesity. Alternative splicing results in multiple transcript variants. Naturally-occurring readthrough transcription between this gene and upstream GeneID:147081 results in transcripts that encode isoforms that share similarity with the products of this gene. [provided by RefSeq, Aug 2016]

LINC02210-CRHR1 (HGNC:):

MAPT-AS1 (HGNC:43738): (MAPT antisense RNA 1) Implicated in Parkinson's disease. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRHR1	NM_004382.5	c.327+403A>G		intron_variant		ENST00000314537.10	NP_004373.2
LINC02210-CRHR1	NM_001256299.3	c.-199+403A>G		intron_variant			NP_001243228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRHR1	ENST00000314537.10	c.327+403A>G		intron_variant		1	NM_004382.5	ENSP00000326060	P1
MAPT-AS1	ENST00000634876.2	n.2593+3740T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.896 AC: 136284 AN: 152174 Hom.: 61131 Cov.: 34

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.925

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.894

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.896 AC: 136382 AN: 152292 Hom.: 61173 Cov.: 34 AF XY: 0.899 AC XY: 66970 AN XY: 74474

Gnomad4 AFR AF: 0.860

Gnomad4 AMR AF: 0.928

Gnomad4 ASJ AF: 0.888

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.971

Gnomad4 FIN AF: 0.923

Gnomad4 NFE AF: 0.892

Gnomad4 OTH AF: 0.895

Alfa AF: 0.896 Hom.: 45362

Bravo AF: 0.895

Asia WGS AF: 0.977 AC: 3398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	9.8
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs242936; hg19: chr17-43899209;